Feedback loop for stimulating nerve tissue downstream of a damaged or severed nerve

ABSTRACT

This document provides methods and materials involved in detecting and delivering neurochemical signals, electrophysiological signals, ions, or combinations thereof within a mammal. For example, systems that can include one or more implantable devices containing probes configured to detect neurochemical signals (e.g., neurotransmitter concentrations), electrical signals, ions, or combinations thereof and one or more implantable devices containing electrodes and/or microfluidic delivery components configured to deliver neurochemical signals (e.g., neurotransmitters), electrical signals, ions, or combinations thereof to one or more locations within a mammal are provided.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No. 16/023,964, filed Jun. 29, 2018, which is a continuation of U.S. application Ser. No. 14/760,011, filed Jul. 9, 2015 (now U.S. Pat. No. 10,029,101), which is a National Stage application under 35 U.S.C. § 371 of International Application No. PCT/US2014/010882, filed Jan. 9, 2014, which claims the benefit of U.S. Provisional Application Ser. No. 61/750,550, filed Jan. 9, 2013. The disclosures of the prior applications are considered part of (and are incorporated by reference in) the disclosure of this application.

BACKGROUND 1. Technical Field

This document relates to methods and materials involved in detecting and delivering neurochemical signals, electrophysiological signals, ions, or combinations thereof within a mammal. For example, this document relates to methods and materials for using an implantable device containing probes to detect neurochemical signals (e.g., neurotransmitter concentrations), electrical signals, ions, or combinations thereof within one region of a mammal's brain and an implantable device containing electrodes and microfluidic delivery components to deliver neurochemical signals (e.g., neurotransmitters), electrical signals, ions, or combinations thereof to another location within the mammal (e.g., in the brain, spinal cord region, peripheral nervous system, or a muscle region within a mammal).

2. Background Information

The brain, spinal cord, and peripheral nervous system use electrical and chemical signaling to control movements and processes within a mammal. In some cases, artificial electrical stimulation can be performed within a mammal's brain to treat certain conditions. For example, deep brain stimulation (DBS) surgery, a neurosurgical intervention procedure, can be used to treat single or multiple disorders, including Parkinson's disease (PD), tremor, dystonia, depression, and chronic pain. Several theories have been proposed to account for the therapeutic action of DBS, some of which are based on the stimulation evoked release of neurotransmitters such as dopamine, glutamate, GABA, and adenosine from proximal and distal brain nuclei.

SUMMARY

This document provides methods and materials involved in detecting and delivering neurochemical signals, electrophysiological signals, ions, or combinations thereof within a mammal. For example, this document provides systems that can include one or more implantable devices containing probes configured to detect neurochemical signals (e.g., neurotransmitter concentrations), electrical signals, ions, or combinations thereof and one or more implantable devices containing electrodes and/or microfluidic delivery components configured to deliver neurochemical signals (e.g., neurotransmitters), electrical signals, ions, or combinations thereof to one or more locations within a mammal.

As described herein, a system provided herein can include an implantable detection device configured to be implanted into a first location within the brain of a mammal. Such an implantable detection device can include one or more probes configured to detect neurochemical signals (e.g., neurotransmitter concentrations), electrical signals, ions, or combinations thereof and can be configured to send information about detected neurochemical signals, electrical signals, and ions. The system also can include an implantable delivery and detection device configured to be implanted into a location outside of the brain of the mammal. For example, an implantable delivery and detection device can be configured to be implanted within a spinal cord region of a mammal with a damaged or severed spinal cord such that the delivery and detection device is located downstream of the damaged or severed spinal cord. Such an implantable delivery and detection device can include one or more electrodes for delivering electrical signals to the mammal's tissue (e.g., nerves or muscle tissue), one or more microfluidic components for delivering chemical signals and/or ions to the mammal's tissue (e.g., nerves or muscle tissue), and one or more probes configured to detect neurochemical signals (e.g., neurotransmitter concentrations), electrical signals, ions, or combinations thereof. Such an implantable delivery and detection device also can be configured to receive information about detected neurochemical signals, electrical signals, and ions sent from the detection device located in the brain and can be configured to send information about detected neurochemical signals, electrical signals, and ions in the region of the delivery and detection device.

Having the ability to detect neurochemical signals, electrical signals, ions, or combinations thereof in one location within a mammal's brain quickly and accurately and to deliver neurochemical signals, electrical signals, ions, or combinations thereof to another location within the mammal's body that is downstream of a damaged or severed nerve (e.g., spinal cord injury) quickly and accurately in response to the detected signals can allow researchers, medical personnel, and patients to reconnect communication across a damaged or severed nerve. Such reconnected communication can allow different combinations of signals to be assessed for the ability to activate particular muscular movements downstream of a damaged or severed nerve in response to a particular detected signal profile within a region of the brain. In some cases, the systems provided herein can be used to create a list of brain signal profiles that represent particular desired or needed muscular movements and a list of delivery signal profiles that have the ability to activate particular muscular movements.

In general, one aspect of this document features a system for detecting signals within the brain of a mammal and delivering signals to nerve tissue downstream of a damaged or severed nerve. The system comprises, or consists essentially of, (a) a first implantable device comprising one or more probes configured to detect neurochemical and electrical signals within a first region of the brain, (b) a second implantable device comprising one or more electrodes configured to deliver electrical signals to the nerve tissue, and (c) a third implantable device comprising one or more electrodes configured to deliver electrical signals to a second region of the brain or one or more microfluidic delivery components configured to deliver neurochemical signals to the second region of the brain, wherein the first implantable device is configured to send information about detected neurochemical and electrical signals directly or indirectly to the second implantable device, wherein the second implantable device is configured to deliver electrical signals and neurochemical signals to the nerve tissue based on the information, and wherein the third implantable device is configured to deliver electrical signals or neurochemical signals to the second region of the brain while or after the second implantable device is delivering electrical signals and neurochemical signals to the nerve tissue. The second implantable device can comprise one or more microfluidic delivery components configured to deliver neurochemical signals to the nerve tissue. The second implantable device can be located within a limb, a diaphragm, a genital region, a bladder, a vascular system, or facial tissue.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Although methods and materials similar or equivalent to those described herein can be used to practice the invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.

The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims.

DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts a system that includes implantable devices for detecting and delivering signals, in accordance with some embodiments.

FIG. 2 depicts a system that includes implantable devices for detecting and delivering signals, in accordance with some embodiments.

FIGS. 3A-D depict probe assemblies including chemical probes, in accordance with some embodiments.

FIGS. 4A-D depict probe assemblies including chemical probes and electrical probes, in accordance with some embodiments.

FIGS. 5A-F depict probe assemblies including chemical probes, electrical probes, and electrodes, in accordance with some embodiments.

DETAILED DESCRIPTION

This document provides methods and materials involved in detecting and delivering neurochemical signals, electrical signals, ions, or combinations thereof within a mammal. For example, this document provides systems that can include one or more implantable devices containing probes configured to detect neurochemical signals (e.g., neurotransmitter concentrations), electrical signals, ions, or combinations thereof and one or more implantable devices containing electrodes and/or microfluidic delivery components configured to deliver neurochemical signals (e.g., neurotransmitters), electrical signals, ions, or combinations thereof to one or more locations within a mammal. In some cases, an implantable device containing a probe can include one or more transmitters and/or one or more processors configured to transmit wirelessly information or instructions about the detected signals to an implantable device containing an electrode and/or microfluidic delivery components. In some cases, an implantable device containing an electrode and/or microfluidic delivery components can include one or more receivers and/or one or more processors configured to receive information or instructions sent from an implantable device containing a probe. The methods and materials provided herein can be used with any appropriate mammal including, without limitation, humans, monkeys, horses, cows, pigs, sheep, goats, dogs, cats, rabbits, rats, and mice.

In some cases, an implantable device containing one or more probes configured to detect neurochemical signals, electrical signals, ions, or combinations thereof can be implanted into a region of a mammal's brain to detect neurochemical signals, electrical signals, ions, or combinations thereof within that region. Examples of neurochemicals that can be detected using the methods and materials provided herein include, without limitation, dopamine, serotonin, adenosine, adenine mono- or tri-phosphate, norepinephrine, GABA, histamine, acetylcholine, glutamate, aspartate, epinephrine, nitric oxide, glycine, trace amines (e.g., tryptamine, phenylethylamine, tyramine, and octopamine), and amino acid-based neuropeptides (e.g., endorphins, enkephalins, and vasopressin). For example, an implantable device containing one or more probes provided herein can include one or more sensors to detect one or more neurochemicals. In some cases, a single sensor can be used to detect a single neurochemical. For example, an implantable device containing one or more probes provided herein can include a first sensor designed to detect dopamine and a second sensor designed to detect glutamate. Another design is to use a singular sensing electrode, and by impressing different voltage ramps, different neurochemicals can be detected using the same sensing electrode at slightly different times.

The methods and materials provided herein can be used to detect any appropriate electrical signal generated within a mammal (e.g., a human). For example, an implantable device containing one or more probes provided herein can include one or more sensors to detect electrical signals within the brain of a mammal.

Examples of ions that can be detected using the methods and materials provided herein include, without limitation, calcium, magnesium, sodium, potassium, protons (pH), iron, copper, chromium, lead, mercury, cobalt, gold, lithium, cesium, barium, zinc, chloride, bicarbonate, phosphate, bromide, iodide, sulfide, oxide, sulfide, oxygen, and fluoride. For example, an implantable device containing one or more probes provided herein can include one or more sensors to detect one or more ions. In some cases, a single sensor can be used to detect a single ion. For example, an implantable device containing one or more probes provided herein can include a first sensor designed to detect calcium and a second sensor designed to detect protons. Another design is to use a singular sensing electrode, and by impressing different voltage ramps, different ions can be detected using the same sensing electrode at slightly different times.

An implantable device containing one or more probes configured to detect neurochemical signals, electrical signals, ions, or combinations thereof can be implanted into any appropriate region of a mammal's brain to detect neurochemical signals, electrical signals, ions, or combinations thereof within that region. For example, an implantable device containing one or more probes configured to detect neurochemical signals, electrical signals, ions, or combinations thereof can be implanted into the cerebral cortex, thalamus, basal ganglia, or brainstem region of a mammal's brain.

In some cases, an implantable device containing one or more probes configured to detect neurochemical signals, electrical signals, ions, or combinations thereof can be configured to send the detected information regarding neurochemical signals, electrical signals, ions, or combinations thereof to a control unit located within or outside of the mammal. For example, an implantable device containing one or more probes can be configured to send the detected information to a computerized control unit having the ability to assess the information for particular signal profiles. In such cases, the computerized control unit can send information about the detected information or about a particular signal profile to one or more other implanted devices (e.g., an implantable devices containing electrodes and/or microfluidic delivery components configured to deliver neurochemical signals, electrical signals, ions, or combinations thereof to one or more locations within the mammal). In some cases, an implantable device containing one or more probes configured to detect neurochemical signals, electrical signals, ions, or combinations thereof can be configured to include a computerized control unit capable of sending information about the detected information or about a particular signal profile to one or more other implanted devices.

In general, an implantable device containing one or more probes configured to detect neurochemical signals, electrical signals, ions, or combinations thereof is used in combination with one or more implantable devices containing one or more electrodes and/or microfluidic delivery components configured to deliver neurochemical signals, electrical signals, ions, or combinations thereof. In some cases, an implantable device containing one or more electrodes and/or microfluidic delivery components configured to deliver neurochemical signals, electrical signals, ions, or combinations thereof can be implanted within a mammal's body to deliver neurochemical signals, electrical signals, ions, or combinations thereof to that region of the mammal's body. Such an implantable device containing one or more electrodes and/or microfluidic delivery components configured to deliver neurochemical signals, electrical signals, ions, or combinations thereof can be configure to receive signals from a computerized control unit capable of sending information. Such information can include, without limitation, information about detected information obtained from an implantable device containing one or more probes configured to detect neurochemical signals, electrical signals, ions, or combinations thereof, information about a particular signal profile obtained from an implantable device containing one or more probes configured to detect neurochemical signals, electrical signals, ions, or combinations thereof, or information about the type and/or duration of signals to deliver. For example, an implantable device containing one or more probes configured to detect neurochemical signals, electrical signals, ions, or combinations thereof can include a computerized control unit that sends a delivery signal profile based on detected information about neurochemical signals, electrical signals, and/or ions within the brain of a mammal to an implantable device containing one or more electrodes and/or microfluidic delivery components configured to deliver neurochemical signals, electrical signals, and/or ions to the mammal. Once such information is received by an implantable device containing one or more electrodes and/or microfluidic delivery components configured to deliver neurochemical signals, electrical signals, and/or ions, that implantable device can deliver neurochemical signals, electrical signals, and/or ions to the mammal according to the information received.

An implantable device containing one or more electrodes and/or microfluidic delivery components configured to deliver neurochemical signals, electrical signals, and/or ions can be implanted into any appropriate region of a mammal's body to deliver neurochemical signals, electrical signals, ions, or combinations thereof to that region. For example, an implantable device containing one or more electrodes and/or microfluidic delivery components can be implanted a region such as the spinal cord region, a dorsal root ganglia, a peripheral nerve, or a muscle such as the diaphragm, bladder, or the like. In some cases, an implantable device containing one or more electrodes and/or microfluidic delivery components can be implanted downstream of a damaged or severed nerve (e.g., damaged or severed spinal cord).

Any appropriate electrical signal can be delivered to a mammal's tissue (e.g., nerve tissue or muscle tissue) when an implanted device containing one or more electrodes and/or microfluidic delivery components is triggered to deliver an electrical signal. For example, continuous electrical stimulation, electrical pulses, sigmoidal pulses, or any user defined pulses can be delivered by an implantable device containing one or more electrodes and optionally one or more microfluidic delivery components.

Any appropriate neurochemical signal or ion can be delivered to a mammal's tissue (e.g., nerve tissue or muscle tissue) when an implanted device containing one or more electrodes and/or microfluidic delivery components is triggered to deliver a neurochemical signal or ion. For example, adenosine, serotonin, norepinephrine, and/or protons can be delivered by an implantable device containing one or more microfluidic delivery components and optionally one or more electrodes. In some cases, an implantable device containing one or more microfluidic delivery components and optionally one or more electrodes can be configured to deliver growth factors such as nerve growth factor, glia derived neurotrophic factor, or epidermal growth factor. For example, growth factors can be delivered to a particular location within a mammal in addition electrical signals, neurochemical signals, and ions.

In some cases, an implantable device containing one or more electrodes and/or microfluidic delivery components configured to deliver neurochemical signals, electrical signals, and/or ions can include one or more probes configured to detect neurochemical signals, electrical signals, ions, or combinations thereof. In such cases, the implantable device can be configured to send the detected information regarding neurochemical signals, electrical signals, ions, or combinations thereof to a control unit located within or outside of the mammal. For example, an implantable device configured to deliver and to detect signals can be configured to send the detected information to a computerized control unit having the ability to assess the information for particular signal profiles. In such cases, the computerized control unit can send information about the detected information or about a particular signal profile to one or more other implanted devices (e.g., a first implantable device containing one or more probes that is located within a first location within the mammal's brain or a second implantable device containing one or more probes that is located within a second location within the mammal's brain). In some cases, an implantable device configured to deliver and to detect signals can be configured to include a computerized control unit capable of sending information about the detected information or about a particular signal profile to one or more other implanted devices.

In some cases, three or more implantable device can be used in combination to create a feedback system. For example, a first implantable device containing one or more probes can be positioned at a first location within the mammal's brain to obtain a first signal profile. Once detected, the signal profile or information about the signals to be delivered based on that signal profile can be sent to a second implantable device containing one or more electrodes and/or one or more microfluidic delivery components that is positioned at a second location within the mammal's body. In some cases, the second location can be a region downstream of a damaged or severed nerve (e.g., a region proximal to a severed nerve). Such a second implantable device can be configured to deliver electrical signals, neurochemical signals, growth factors, and/or ions based on the information received from the first implantable device or a computerized control unit in communication with the first implantable device. In some cases, the second implantable device can be configured to detect electrical signals, neurochemical signals, and/or ions within the region where it is implanted. In addition, the second implantable device can be configured to send information about the delivered signals and/or any detected electrical signals, neurochemical signals, and/or ions to the control unit or to a third implantable device. In some cases, the third implantable device can be located within the brain of the mammal at a location that is different from the location of the first implantable device. The third implantable device can be configured to have one or more electrodes and/or one or more microfluidic delivery components configured to deliver neurochemical signals, electrical signals, and/or ions to the mammal's brain. Delivery of these neurochemical signals, electrical signals, and/or ions to the brain can complete a communication loop that originated within a first location of the brain, flowed to a location outside the brain (e.g., a location downstream of a damaged or severed nerve), and flowed back to a second location within the brain.

An implantable device of a system provided herein can include any combination of (a) one or more probes configured to detect neurochemical signals, electrical signals, ions, or combinations thereof, (b) one or more electrodes configured to deliver electrical signals, and (c) one or more microfluidic delivery components configured to deliver neurochemical signals, ions, and/or growth factors. Examples of probes configured to detect neurochemical signals, electrical signals, ions, or combinations thereof include those probes described in U.S. Patent Application Publication No. 2012/0165634. Examples of electrodes configured to deliver electrical signals include those electrodes described in U.S. Patent Application Publication No. 2012/0165634. In some cases, electrical signals can be provided using an electrode such as a neurostimulator (e.g., a Medtronic™ Soletra or Kinetra neurostimulator). Examples of microfluidic delivery components that can be configured to deliver neurochemical signals, growth factors, and/or ions include, without limitation, microfluidic tubes, channels, valves, pathways, input ports, storage regions, and output ports.

In some cases, multiplexed arrays of sensing probes and/or stimulation electrodes can be used. In some cases, a 10×10 electrode array, offering about 100 points in a plane, can be used, thereby covering a substantial volume area. The array can be sized such that a substantial volume can be stimulated by choice, and the activity can be detected in the volume. Time mapping of activity or effect can be carried out using an array. By multiplexing the detection or delivery stimulation, the overhead of data bandwidth and the amount of support electronics can be decreased.

In some cases, an implantable device provided herein can include a single electrode probe for fast scan cyclic voltammetry (FSCV). The single electrode probe can include independent areas (e.g., two independent areas) of active electrode such as pyrolytic carbon or carbon fiber, that, by varying the FSCV impressed voltage, signals representing different neurochemicals can be determined. If the areas are too close together, which would cause interference, the signals can be multiplexed such that the signal is detected quasi simultaneously by measuring one chemical directly after the first chemical was detected. In some cases, an implantable device provided herein can be used to determine the effect of stimulation. Stimulation of two different areas can produce release of different neurochemicals (such as histamine, adenosine, glutamate, and dopamine), and the ratio or absolute amount changes can provide a physiologic effect of interest.

In some cases, one or more chemicals (e.g., dopamine, adenosine, serotonin, and norepinephrine) can be detected using various scan waveforms in FSCV applied to one or more probes.

Referring now to FIG. 1, in some embodiments, a system 10 can include an implantable device 12 containing one or more probes configured to detect neurochemical signals, electrical signals, ions, or combinations thereof. Implantable device 12 can include a control unit and can be in wireless communication with an implantable device 14 containing one or more electrodes configured to deliver electrical signals and/or one or more microfluidic delivery components configured to deliver neurochemical signals, growth factors, and/or ions. In some cases, implantable device 14 can include one or more probes configured to detect neurochemical signals, electrical signals, ions, or combinations thereof. Implantable device 14 can include a control unit and can be in wireless communication with an implantable device 16 containing one or more electrodes configured to deliver electrical signals and/or one or more microfluidic delivery components configured to deliver neurochemical signals, and/or ions. In some cases, implantable device 12 can be positioned within a first location within a mammal's brain, implantable device 14 can be positioned within the mammal's body downstream of a damaged or severed nerve (e.g., proximal to the downstream point of the nerve injury), and implantable device 16 can be positioned within a second location within the mammal's brain.

Referring now to FIG. 2, in some embodiments, a system 20 can include an implantable device 12 containing one or more probes configured to detect neurochemical signals, electrical signals, ions, or combinations thereof, an implantable device 14 containing one or more electrodes configured to deliver electrical signals and/or one or more microfluidic delivery components configured to deliver neurochemical signals, growth factors, and/or ions, and an implantable device 16 containing one or more electrodes configured to deliver electrical signals and/or one or more microfluidic delivery components configured to deliver neurochemical signals, and/or ions. In some cases, implantable device 14 can include one or more probes configured to detect neurochemical signals, electrical signals, ions, or combinations thereof. Each of implantable device 12, implantable device 14, and implantable device 16 can include a control unit and can be in wireless communication with a processing unit 18. Processing unit 18 can be configured to send information to and receive information from each of implantable device 12, implantable device 14, and implantable device 16.

Processing unit 18 can be implanted within the mammal containing implantable device 12, implantable device 14, and implantable device 16 or can be located outside of the mammal containing implantable device 12, implantable device 14, and implantable device 16. In some cases, processing unit 18 can be a hand held communicating device, a personal computing workstation, a server, or the like, and can wirelessly communicate with a display configured to display information indicative of data received by processing unit 18.

In some cases, implantable device 12 can include one or more probes in communication with one or more control units that, for example, can receive information from the individual probes, prepare the data for transmission, and telemeter the prepared data to processing unit 18. In some cases, the control units can receive data from processing unit 18. For example, processing unit 18 can instruct one or more of the control units of implantable device 12 to transmit data from one or more of the probes of implantable device 12 to processing unit 18. In another example, processing unit 18 can instruct individual control units of implantable device 14 to activate one or more electrodes of implantable device 14 to stimulate surrounding tissue and/or to activate one or more microfluidic delivery components to deliver neurochemical signals, and/or ions to surrounding tissue.

Referring now to FIGS. 3A-D, in some embodiments, an implantable device provided herein can include one or more probe assemblies 200 where each probe assembly 200 can include one or more probes configured to measure a single chemical. In this configuration, a single probe assembly 200 can advantageously measure the level of more than a single chemical. Exemplary measurements performed by chemical probes can include pH level, the concentration of neurochemicals (e.g., dopamine, serotonin, adenosine, norepinephrine, GABA, histamine, acetylcholine, glutamate, and the like), enzymatic activity, electrophsiological activity, and the like. An individual probe assembly 200 can include one or more retractable and advanceable probes such as side chemical probes 210 and distal chemical probes 220 (FIG. 3A). In some embodiments, probe assembly 200 can include one or more chemical probes 230 bundled within an interior lumen of probe assembly 200 (FIG. 3B). Probe assembly 200 can include one or more chemical ring probes 240 around the circumference of probe assembly 200 (FIG. 3C). In some embodiments, probe assembly 200 can include a central lumen through which one or more chemical probes 250 pass and further extend beyond the distal tip of probe assembly 200 (FIG. 3D).

Referring now to FIGS. 4A-D, in some embodiments, an implantable device provided herein can include one or more probe assemblies 300 where each probe assembly 300 can include one or more chemical probes (e.g., chemical probes of the type described in connection with FIG. 3A-D, and the like) and one or more electrical probes configured to measure a single electrophysiological signal. Exemplary measurements performed by electrical probes can include EEG, EMG, EOG, and the like. An individual probe assembly 300 can include one or more retractable and advanceable probes such as the side chemical probe 210, one or more side electrical probes 315, the one or more distal chemical probes 220, and one or more distal electrical probes 325 (FIG. 4A). In some embodiments, probe assembly 300 can include one or more chemical probes 230 and one or more electrical probes 335 bundled within an interior lumen of probe assembly 300 (FIG. 4B). Probe assembly 300 can include one or more of chemical ring probes 240 and one or more electrical ring probes 345 around the circumference of probe assembly 300 (FIG. 4C). In some embodiments, probe assembly 300 can include a central lumen through which one or more chemical probes 250 and one or more electrical probes 355 pass and further extend beyond the distal tip of probe assembly 300 (FIG. 4D). Probe assembly 300 can include one or more probes (e.g., chemical probes 360, electrical probes (not shown), and the like) mounted on the outside wall of and external to probe assembly 300 (FIG. 4D).

Referring now to FIGS. 5A-F, in some embodiments, an implantable device provided herein can include one or more probe assemblies 400 where each probe assembly 400 can include one or more probes (e.g., probes of the types described in connection with FIGS. 3A-D, FIGS. 4A-D, and the like) and one or more electrodes 405 that can provide an electrical signal to surrounding tissues. Exemplary electrodes 405 can be used to provide electrical signals to nerve or muscle tissue within a mammal downstream of a damaged or severed nerve. An individual probe assembly 400 can include a side chemical probe 210 and a side electrical probe 315 that extend from a sidewall of electrode 405 (FIG. 5A). In some embodiments, probe assembly 400 can include one or more chemical probes 330 and electrical probes 335 bundled around the exterior of electrode 405 and contained, at least partially, within an outer housing 402 (FIG. 5B). Probe assembly 400 can include one or more chemical ring probes 240 and one or more electrical ring probes 345 around the circumference of electrode 405 (FIG. 5C). In some embodiments, probe assembly 400 can include one or more probes (e.g., a chemical probe 360, an electrical probe (not shown), and the like) mounted on the outside wall of and external to electrode 405 (FIG. 5D).

Referring now to FIG. 5E, in some embodiments, a probe assembly 400 can include an electrode 405 with a central lumen 407 through which one or more probes (e.g., electrical probes 465, chemical probes (not shown), and the like) can pass. Referring now to FIG. 5F, in some embodiments, a probe assembly 400 can include an electrode 405 with a central lumen 407 through which one or more of chemical probes 250 and one or more of electrical probes 355 pass and further extend beyond the distal tip of electrode 405. In some cases, a probe assembly can include one or more of ring probes 240 and 345 around the circumference of electrode probe 405 and one or more probes 210 and 215 that extend from the sidewall.

Other Embodiments

It is to be understood that while the invention has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims. 

What is claimed is:
 1. A system for detecting signals within a brain of a mammal and delivering signals to nerve tissue downstream of a damaged or severed nerve of said mammal, wherein said system comprises: (a) a first implantable device comprising one or more probes configured to detect signals within a first region of said brain, (b) a second implantable device configured (i) to deliver stimulus to said nerve tissue downstream of said damaged or severed nerve and (ii) to detect signals from a tissue of said mammal proximate to said nerve tissue, and (c) a third implantable device comprising one or more electrodes configured to deliver electrical signals to a second region of said brain or one or more microfluidic delivery components configured to deliver neurochemical signals to said second region of said brain, wherein said first implantable device is configured to send first information about detected signals within said first region of said brain directly or indirectly to said second implantable device, wherein said second implantable device is configured (i) to deliver stimulus to said nerve tissue downstream of said damaged or severed nerve based on said first information and (ii) to send second information about detected signals from said tissue proximate to said nerve tissue directly or indirectly to said third implantable device, and wherein said third implantable device is configured to deliver electrical signals or neurochemical signals to said second region of said brain based on said second information.
 2. The system of claim 1, wherein the second implantable device further comprises one or more microfluidic delivery components configured to deliver neurochemical signals to said nerve tissue.
 3. The system of claim 1, wherein said second implantable device is adapted to be located within a limb, a diaphragm, a genital region, a bladder, a vascular system, or facial tissue.
 4. The system of claim 1, wherein said third implantable device is further configured to deliver electrical signals or neurochemical signals to said second region of said brain based on said second information while or after said second implantable device is delivering stimulus to said nerve tissue downstream of said damaged or severed nerve.
 5. The system of claim 1, wherein said first information about detected signals within said first region of said brain describes a level of at least one neurochemical or ion within said first region of said brain.
 6. The system of claim 1, wherein said first information about detected signals within said first region of said brain describes electrical activity within said first region of said brain.
 7. The system of claim 1, wherein said stimulus that said second implantable device is configured to deliver to said nerve tissue downstream of said damaged or severed nerve comprises electrical stimulus, neurochemical stimulus, ion stimulus, or growth factor stimulus.
 8. The system of claim 1, wherein said second information about detected signals from said tissue proximate to said nerve tissue describes at level of at least one neurochemical or ion proximate to said nerve tissue, or electrical activity proximate to said nerve tissue.
 9. A method, comprising: receiving, by a first device implanted in a mammal, first information about signals indicative of a condition of a first upstream region of a nervous system of said mammal, wherein said signals indicative of said condition of said first upstream region of said nervous system were detected by a second device proximate to said first upstream region; delivering, by said first device, stimulus to tissue downstream of a damaged or severed nerve of said mammal; detecting, by said first device, signals indicative of a condition of said tissue downstream of said damaged or severed nerve; and transmitting, from said first device, second information about said signals indicative of said condition of said tissue downstream of said damaged or severed nerve, wherein a third device proximate to a second upstream region of said nervous system is configured to receive said second information and to deliver stimulus to said second upstream region based on said second information.
 10. The method of claim 9, wherein said first information describes a level of at least one neurochemical or ion within said first upstream region of said nervous system, or electrical activity within said first upstream region.
 11. The method of claim 9, wherein said second information describes a level of at least one neurochemical or ion proximate to said tissue, or electrical activity proximate to said tissue.
 12. The method of claim 9, wherein delivering stimulus to said tissue downstream of said damaged or severed nerve of said mammal comprises applying electrical stimulus to said tissue.
 13. The method of claim 9, wherein delivering stimulus to said tissue downstream of said damaged or severed nerve of said mammal comprises administering a neurochemical, an ion, or a growth factor to said tissue. 